The aim of this study was to resolve discordant reports of increased versus decreased sciatic nerve blood flow obtained by noninvasive (e.g. microspheres) versus surgically invasive methods (e.g. hydrogen clearance and laser Doppler flowmetry), respectively. Blood flow was assessed in both sciatic nerves by injecting 10um 46Sc-microspheres in male Sprague-Dawley rats with streptozotocin (50 mg/kg bwt) diabetes of 2-3 weeks duration. One sciatic nerve was carefully exposed (in rats anesthetized with methoxyflurene or thiopental) by blunt dissection without touching the nerve; blood flow (ml/g/min) was assessed in unexposed nerves and in surgically exposed nerves after 0, 15, 30, 60, and 120 min. The side of exposure and exposure time were selected randomly. Diabetic rats had lower body weight, higher plasma glucose and higher plasma b-hydroxybutyrate than age-matched control rates. Mean arterial blood pressure, artial PO2, and pH were in the normal range and did not differ for controls and diabetics. In previously unexposed nerves total blood flow was 20% higher in diabetics than in controls. Endoneurial and epineurial blood flow also were significantly higher in diabetics than in controls. Fifteen minutes after surgical exposure blood flow decreased in diabetics and in controls. Blood flow then increased progressively by 2 to 3 fold with time in surgically exposed nerves to values at 2 h of 0.215 +/- 0.029 in diabetics and 0.292 +/- 0.037 in controls. Endoneurial and epineurial blood flow were similarly affected. Thus nerve blood flow was increased 20% by diabetes in intact nonexposed nerves but was 26% lower in diatetics versus controls 2 hours following surgical exposure. These observations are consistent with numerous reports that vasodilatory responses to various stimuli are impaired by diabetes. They also indicate that techniques requiring prior surgical exposure of the nerve are unsuitable for assessing nerve blood flow.